Inhibition of Hepatitis B Virus by Hammerhead Ribozyme Targeted to the Poly(A) Signal Sequence in Cultured Cells
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Ying Feng
Abstract
The deviant poly(A) signal of hepatitis B virus (HBV) not only controls the formation of the 3 end of all the viral RNA, but is also crucial for HBV replication. Hence, a cisreleasing hammerhead ribozyme (RzA) targeted to the poly(A) signal region of HBV subtype adr was investigated for its antiviral effects. In vitro, RzA cleaved HBV RNA at its target site up to 70%, while the disabled ribozyme (dRzA), which had a onebase mutation in the catalytic site, did not cleave the target RNA at all. When the ribozymes were cotransfected into HepG2 cells with the HBV genomecontaining plasmid p3.6II, the wildtype ribozyme RzA could effectively decrease HBV RNA levels and inhibit HBV replication, whereas its disabled form, dRzA, had much weaker effects, indicating that the active catalytic domain of the hammerhead ribozyme could markedly increase the extent of antisensemediated inhibition. In addition, there was a gradient of effectiveness: the higher the amount of released ribozyme, the more the reduction in target HBV RNA in cells as well as progeny DNA reduction. These results suggest the possibility of the hammerhead ribozyme RzA to be used for the gene therapy of HBV infection.
Copyright © 2001 by Walter de Gruyter GmbH & Co. KG
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- Intracellular Bacteria as Targets and Carriers for Vaccination
- Bacteria-Mediated Transfer of Eukaryotic Expression Plasmids into Mammalian Host Cells
- Revealing the Potential of DNA-Based Vaccination: Lessons Learned from the Hepatitis B Virus Surface Antigen
- Progress toward a Malaria Vaccine: Efficient Induction of Protective Anti-Malaria Immunity
- Peptide Vaccines and Peptide Libraries
- Defined Synthetic Vaccines
- Antimicrobial Peptides: Properties and Applicability
- G-Quadruplex DNA Structures Variations on a Theme
- The Role of Heat Shock Proteins and Their Receptors in the Activation of the Immune System
- Transcriptional Repression Mediated by the KRAB Domain of the Human C2H2 Zinc Finger Protein Kox1/ZNF10 Does Not Require Histone Deacetylation
- Structure and Evolution of 4-Coumarate:Coenzyme A Ligase (4CL) Gene Families
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- Chemical Accessibility of 18S rRNA in Native Ribosomal Complexes: Interaction Sites of mRNA, tRNA and Translation Factors
- C-Terminal Peptides of Interleukin-6 Modulate the Expression of junB Protooncogene and the Production of Fibrinogen by HepG2 Cells
- Proteome Analysis by Three-Dimensional Protein Separation: Turnover of Cytosolic Proteins in Hepatocytes
- Structural Intermediates in the Putative Pathway from the Cellular Prion Protein to the Pathogenic Form
- Local Variability of the Phosphoglycerate Kinase-Triosephosphate Isomerase Fusion Protein from Thermotoga maritima MSB 8
- Epigenetics of Latent Epstein-Barr Virus Genomes: High Resolution Methylation Analysis of the Bidirectional Promoter Region of Latent Membrane Protein 1 and 2B Genes
- The Cytosine N4-Methyltransferase M.PvuII Also Modifies Adenine Residues
- Expression of the Human Menkes ATPase in Xenopus laevis Oocytes
Articles in the same Issue
- Vaccine Development: from Empirical Medicine to Molecularly Designed Therapy
- Dendritic Cells for Specific Cancer Immunotherapy
- Intracellular Bacteria as Targets and Carriers for Vaccination
- Bacteria-Mediated Transfer of Eukaryotic Expression Plasmids into Mammalian Host Cells
- Revealing the Potential of DNA-Based Vaccination: Lessons Learned from the Hepatitis B Virus Surface Antigen
- Progress toward a Malaria Vaccine: Efficient Induction of Protective Anti-Malaria Immunity
- Peptide Vaccines and Peptide Libraries
- Defined Synthetic Vaccines
- Antimicrobial Peptides: Properties and Applicability
- G-Quadruplex DNA Structures Variations on a Theme
- The Role of Heat Shock Proteins and Their Receptors in the Activation of the Immune System
- Transcriptional Repression Mediated by the KRAB Domain of the Human C2H2 Zinc Finger Protein Kox1/ZNF10 Does Not Require Histone Deacetylation
- Structure and Evolution of 4-Coumarate:Coenzyme A Ligase (4CL) Gene Families
- Inhibition of Hepatitis B Virus by Hammerhead Ribozyme Targeted to the Poly(A) Signal Sequence in Cultured Cells
- Chemical Accessibility of 18S rRNA in Native Ribosomal Complexes: Interaction Sites of mRNA, tRNA and Translation Factors
- C-Terminal Peptides of Interleukin-6 Modulate the Expression of junB Protooncogene and the Production of Fibrinogen by HepG2 Cells
- Proteome Analysis by Three-Dimensional Protein Separation: Turnover of Cytosolic Proteins in Hepatocytes
- Structural Intermediates in the Putative Pathway from the Cellular Prion Protein to the Pathogenic Form
- Local Variability of the Phosphoglycerate Kinase-Triosephosphate Isomerase Fusion Protein from Thermotoga maritima MSB 8
- Epigenetics of Latent Epstein-Barr Virus Genomes: High Resolution Methylation Analysis of the Bidirectional Promoter Region of Latent Membrane Protein 1 and 2B Genes
- The Cytosine N4-Methyltransferase M.PvuII Also Modifies Adenine Residues
- Expression of the Human Menkes ATPase in Xenopus laevis Oocytes